• Novel Mechanism Designed to Reduce Gastrointestinal Serotonin Production

The Woodlands, Texas, January 12, 2009 – Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX), a biopharmaceutical company focused on discovering and developing breakthrough treatments for human disease, announced today that it has initiated a Phase 2 clinical trial of LX1031, the company’s oral drug candidate for irritable bowel syndrome (IBS).  Lexicon has three additional drug candidates progressing through various stages of clinical development, including LX1032 for carcinoid syndrome, LX2931 for rheumatoid arthritis, and LX4211 for diabetes.

“Patients with IBS have limited treatment options and are in need of safer, more effective therapies,” said Philip M. Brown, M.D., J.D., senior vice president of clinical development at Lexicon.  “LX1031 is intended to treat symptoms associated with IBS, including diarrhea and abdominal discomfort, by operating through an important new mechanism to reduce serotonin levels locally in the gastrointestinal tract.”

The Phase 2 clinical trial, which began at the end of December 2008, is designed as a four-week, randomized, double-blind, placebo-controlled study to evaluate the safety and tolerability of LX1031 and its effects on symptoms associated with IBS.  The study will include 150 patients with either diarrhea-predominant IBS or mixed IBS.  Two dose levels will be evaluated:  a 250 mg dose and a 1,000 mg dose, each administered four times daily.  The endpoints will include assessments of the effects of LX1031 on specific symptoms associated with IBS, as well as a global assessment of adequate relief.

About LX1031
LX1031 is an oral drug candidate for IBS and other gastrointestinal (GI) disorders.  LX1031 was developed by Lexicon’s research team, which also identified its target as a key control point for the regulation of peripheral serotonin levels.  LX1031 is designed to treat symptoms associated with IBS by decreasing the production of serotonin in the GI tract without affecting serotonin levels in the brain.  In Phase 1 clinical trials, all dose levels were well tolerated, with no dose-limiting toxicities observed, and LX1031 was shown to reduce levels of 5-HIAA, a biomarker of serotonin production. 

LX1031 is being developed in a product development collaboration with Symphony Capital Partners, L.P. and its co-investors.

About Irritable Bowel Syndrome
Irritable bowel syndrome is a disorder most commonly characterized by cramping, abdominal pain, bloating, constipation or diarrhea.  Symptoms of IBS are believed to be mediated through serotonin, which has been shown to play an important role in modulating motility and signaling feelings of GI discomfort to the brain.

About Lexicon
Lexicon is a biopharmaceutical company focused on discovering and developing breakthrough treatments for human disease.  Lexicon currently has five drug candidates in development for autoimmune disease, carcinoid syndrome, diabetes, glaucoma and irritable bowel syndrome, all of which were discovered by the company’s research team.  Lexicon’s goal is to advance 10 drug candidates into human clinical trials by the end of 2010, the strategic objective of its 10TO10 program.  The company has used its proprietary gene knockout technology to identify more than 100 promising drug targets.  Lexicon has applied small molecule chemistry and antibody technology to these biologically-validated targets to create its extensive pipeline of clinical and preclinical programs.  For additional information about Lexicon and its programs, please visit www.lexpharma.com.

Safe Harbor Statement
This press release contains “forward-looking statements,” including statements relating to Lexicon’s clinical development of LX1031 and the potential therapeutic and commercial potential of LX1031.  This press release also contains forward-looking statements relating to Lexicon’s growth and future operating results, discovery and development of products, strategic alliances and intellectual property, as well as other matters that are not historical facts or information.  All forward-looking statements are based on management’s current assumptions and expectations and involve risks, uncertainties and other important factors, specifically including those relating to Lexicon’s ability to successfully conduct clinical development of LX1031 and preclinical and clinical development of its other potential drug candidates, advance additional candidates into preclinical and clinical development, obtain necessary regulatory approvals, achieve its operational objectives, obtain patent protection for its discoveries and establish strategic alliances, as well as additional factors relating to manufacturing, intellectual property rights, and the therapeutic or commercial value of its drug candidates,  that may cause Lexicon’s actual results to be materially different from any future results expressed or implied by such forward-looking statements.  Information identifying such important factors is contained under “Factors Affecting Forward-Looking Statements” and “Risk Factors” in Lexicon’s annual report on Form 10-K for the year ended December 31, 2007, as filed with the Securities and Exchange Commission.  Lexicon undertakes no obligation to update or revise any such forward-looking statements, whether as a result of new information, future events or otherwise.